Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q7/00—Preparations for affecting hair growth
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
  • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/63—Steroids; Derivatives thereof

Definitions

• the present invention relates to the treatment of scalp hair loss and balding in women.
• This is a distressing condition which can affect women at the pre-, peri- post-menopause who have not previously experienced significant hair loss.
• thinning hair is not a socially acceptable condition in women, as it may be in men after a certain age, the condition can cause not merely distress but severe psyschological symtoras in women involving feelings of loss of femininity and self confidence, depression and inability to concentrate of anything except the prospect of impending baldness with mounting embarrassment.
• menopausal symptoms Associated with the menopause, a number of so-called “menopausal symptoms” may be experienced by a patient. It has been found that the present treatment, designed for arresting hair loss, also alleviates these menopausal symptoms, and hence is also suitable for use in long-term hormonal replacement therapy.
• the present invention provides a pharmaceutical formulation for use in treating female scalp hair loss or in hormonal replacement therapy which comprises medroxyprogesterone acetate or its pharmacologically-active equivalent and at least one oestrogen, wherein when prepared in unit dosage form the formulation is adapted to administer at least 1mg and not more than 500mg of medroxyprogesterone acetate or its pharmacologically-active equivalent per month, with the proviso that the said equivalent is not cyproterone acetate.
• Medroxyprogesterone acetate is a synthetic progesterone-like preparation (17 alpha hydroxy - 6 alpha - methyl - delta 4 - pregnen-3, 20 dione - 17 alpha acetate) conveniently referred to as MPA. It has been used previously (as Provera) for the management of functional uterine bleeding, certain hormone dependent neoplasms (malignant diseases) such as endometrial carcinoma, hypernephroma, cancer of prostate.
• scalp hair loss proceeding to baldness in women at the pre-, peri-, post-menopause can be arrested with the growth of new hair using a combination of at least one oestrogen with medroxyprogesterone acetate wherein, when prepared in unit dosage form, the formulation is adapted to administer at least 1mg and not more than 500mg of MPA per month.
• the invention further provides, in combination, a pharmaceutical formulation of the invention, a container therefor, and instructions for the use of the pharmaceutical formulation in the treatment of female scalp hair loss or in hormonal replacement therapy.
• the formulations of the present invention may be designed for oral or parenteral administration. Although the formulations could be for administration by injection, they will most conveniently be for oral administration e.g. as tablets, capsules or solutions or suspensions.
• They may generally be formulated for any of the known routes of pharmaceutical administration.
• a formulation for oral administration will contain from 1 to 50mg, preferably 5 to l0mg, of MPA per unit dosage form e.g. per tablet.
• the identity of the oestrogen used is not critical. Ethinyloestradiol is preferred.
• the oestrogen is present to provide a contraceptive effect, and in addition to provide the beneficial effect of raising plasma sex hormone binding globulin (SHBG) levels thereby diminishing free (biolofically- active) testosterone and other androgen levels.
• a suitable dose rate for ethinyloestradiol would be 10-60 ⁇ g per day orally, preferably about 40ug.
• the treatment of female scalp hair loss will preferably involve the administration of medroxyprogesterone acetate and the oestrogen in a cyclic manner.
• the oestrogen alone will be administered, while in the second part of the cycle both oestrogen and MPA will be administered. This is followed preferably by no treatment to allow for withdrawal bleeding.
• the cycle length is 28 days in accordance with normal contraceptive practice.
• a possible oral dosage regimen would therefore be: Ethinyloestradiol I0-6- ⁇ g daily for 28 days of each cycle;
• Ethinyloestradiol at 30-40 ⁇ g daily for the first 21 days of each cycle and;
• oestrogen and MPA for administration on the same day may conveniently be formulated together as a formulation according to the invention, they can equally well be taken separately. In either case it will be advantageous if the two different types of daily dose, namely oestrogen plus MPA or oestrogen alone are put up in a calendar pack as is the normal practice with contraceptive tablets.
• tablets containing neither active ingredients can be provided for the days when neither ingredient is to be taken.
• the present invention provides a calendar pack containing pharmaceutical formulation doses for use in treating female scalp hair loss or in hormonal replacement therapy, comprising spaced locations corresponding to days of a menstrual cycle, dosage forms in a first series of said locations providing at each location of the series a daily dose of an oestrogen in pharmaceutically-administrable form without medroxyprogesterone acetate or its pharmacologically-active equivalent, and dosage forms at a second series of locations following the first series providing a daily dose of the oestrogen and a daily dose of medroxyprogesterone acetate or its pharmacologically-active equivalent in pharmaceutically-administrable form, wherein the total dosage of medroxyprogesterone acetate or its equivalent in the pack is at least 1mg and not more than 500mg per cycle, with the proviso that the said equivalent is not cyproterone acetate.
• Such pack would be a bubble pack of the conventional kind having a tablet or other dosage form contained in a bubble at each of a series of space locations, normally positioned in a closed loop running round the edge of the pack.
• the locations may be numered, normally 1 to 28.
• the first series of bubbles may contain only one tablet or other dosage form per location containing oestrogen but not MPA.
• the first series of bubbles containing oestrogen only will preferably correspond to up to the first 21 days, e.g. the first 16 days of a 28 day cycle.
• the second series of locations may then contain either one tablet or other dosage form containing both active ingredients or a pair of tablets or other dosage forms per location, one containing oestrogen and the other MPA. Where two dosage forms are provided they may of course be put in separate bubbles at the same day's location.
• the second series may comprise enough locations to correspond to up to the first 27 days of a cycle, preferably from the 16th to the 21st day. If further locations are provided, they may be empty so that they can simply be burst in turn to mark the day's passing or may contain a dosage form containing neither active ingredient.
• topical preparations may enhance the effects of systemic preparations leading to the possible reduction in the dose of either the topical or systemic preparations to produce a synergistic therapeutic effect. For this reason it may be possible for the lower limits of the doses described previously to be reduced while maintaining the effectiveness of the preparations (systemic and topical) in the arrest and reversal of the common baldness process. Such a combination of therapy would be of considerable practical clinical value in allowing the minimum effective dose of treatment to be used.
• Premarin (Ayerst) containing conjugated oestrogens (equine) 0.625mg or 1.25mg taken for 21 days starting on the 5th day of menstruation and then 7 tablet-free days.
• Premarin containing conjugated oestrogens (equine) 0.625mg plus Duphaston (Duphar) dydrogesterone 10mg daily for 7 days from day 14.
• Ovranette containing ethinyloestradiol 30 ⁇ g daily for 21 days combined with levonorgestrel 150 ⁇ g daily for 21 days.
• Ovysmen Ortho-Cilag containing ethinyloestradiol 35 ⁇ g daily for 21 days with norethisterone 0.5mg for 21 days.
• Norgeston Norgeston (Schering) containing levonorgestrel 30 ⁇ g continuously.
• Ethinyl-oestradiol 30 ⁇ g - 40ug daily for 21 days of each cycle.
• MPA 5mg or 10mg daily from days 16 to 21 of the menstrual cycle.
• each patient reported an improvement in hair condition, reduced greasiness and reduction in hair fall and an improvement in general wellbeing.
• Each patient also reported subsequently increased new hair growth and in particular the full growth previously of fine short hairs at the frontal margin.
• the hair line had stopped receding and had moved forward with the growth of new hair. Treatment continued over 2-4 years with regular withdrawal bleeds, no pregnancies and with the retention of the hair growth achieved.
• MPA can be replaced in the formulations of the present invention by any pharmacologically-active thereof at a corresponding dosage level.
• any anti-androgen which has a progesterone-like action similar to MPA locally on scalp hair follicles, whilst at the same time does not significantly reduce SHBG levels.
• Suitable equivalents are allyloestrenol and gestronol.
• Hydroxprogesterone and dydrogesterone may be effective in some patients, but the latter only if the local dosage is high enough and certainly higher than 10 x 7 i.e. 70mg per month described above which was administered systemically.
• Cyproterone acetate is an equivalent of MPA, but since formulations similar to those of the present invention are described and claimed separately in my co-pending application No. (Agents' Ref: )CPA formulations are specifically excluded from the scope of this application.
• Preparation 1 One or more of:
• vasodilators applied topically or given systemically could be included in the Invention.
• the nature of the vasodilators is not critical.
• Cyclic GMP Sodium 0.1% (range 0.0000000001-20%) N2 , 2-O-Dibutyryl Guanosine 3, 5, Cyclic Monophosphate (a long acting synthetic form of Cyclic GMP) 0.01% (range 0.0000000001-20%)
• Thymidine 3 Cyclic Monophosphate, Diphosphate, Triphosphate Uridine 3, 5, Monophosphate, Diphosphate,
• Shunt or the Tricarboxylic Acid cycle to include: One or more of:
• Hexokinase 1,000 IU/L (range 1-100,000)
• Desogestrel 0.1% (range 0.001-20%)
• Lynoestrenol 0.1% (range 0.001-20%)
• Norethisterone 0.1% (range 0.001-20%)
• Progesterone 0.1% (range 0.001-20%)
• Testolactone 0.1% (range 0.001-20%) Danazol 0.1% (range 0.001-20%)
• topical preparations as set out above are administered in addition to the systemic cyclical anti-androgen therapy as described in the Invention
• Triidothyronine as the sodium salt given orally in the range of 1ug-300ug daily, more preferable 20ug three times daily
• the topical preparations as set out above are administered in addition to the systemic cyclical anti-androgen therapy as described in the Invention
• patients have reported that prior to the addition of the topical preparations they would normally cut their hair each 2-3 months to maintain the same style.
• the addition of the above preparations has resulted in hair being required to be cut each 4-6 weeks to maintain the same hair style.
• the rate of growth is increased particularly in the temporal and occipital areas witn an increase in rate of growth in these areas being noted before that in the frontal and vertex regions.
• the rate of hair growth has increased by approximately 25-200% during the first 3-6 months of treatment.

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Epidemiology (AREA)
• Pharmacology & Pharmacy (AREA)
• Medicinal Chemistry (AREA)
• Chemical & Material Sciences (AREA)
• Birds (AREA)
• Dermatology (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicines Containing Material From Animals Or Micro-Organisms (AREA)
• Steroid Compounds (AREA)
• Cosmetics (AREA)

Priority Applications (1)

Applications Claiming Priority (2)

Publications (1)

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Family Applications (1)

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Cited By (2)

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Citations (3)

• 1984
  • 1984-05-22 GB GB848413069A patent/GB8413069D0/en active Pending
• 1985
  • 1985-05-21 GR GR851239A patent/GR851239B/el unknown
  • 1985-05-21 ZA ZA853844A patent/ZA853844B/xx unknown
  • 1985-05-22 PT PT80510A patent/PT80510B/pt unknown
  • 1985-05-22 JP JP60502447A patent/JPS61502190A/ja active Pending
  • 1985-05-22 EP EP85303623A patent/EP0163489A1/en not_active Withdrawn
  • 1985-05-22 WO PCT/GB1985/000218 patent/WO1985005272A1/en not_active Ceased
  • 1985-05-22 AU AU44074/85A patent/AU4407485A/en not_active Abandoned
• 1986
  • 1986-01-21 NO NO860204A patent/NO860204L/no unknown
  • 1986-01-22 DK DK32486A patent/DK32486A/da not_active Application Discontinuation

Patent Citations (3)

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